Day 14 - 06/10/14 Flashcards
Where do you find Class 2 cells?
Antigen Presenting Cells (APC)
Dendritic Cells
Macrophages
B Cells
Where do you find Class 1 cells?
All NUCLEATED cells
Which cells are professional antigen presenting cells?
Dendritic Cells
Macrophages
B Cells
What are the TWO types of ways ANTIGENS are acquired by APCs?
Endogenous (Class 1)
Exogeneous (Class 2)
Where do Class 1 Antigens get presented to?
CD8+ Cytotoxic T Cells
Where do Class 2 Antigens get presented to?
CD4+ T Helper Cells
How do Class 1 molecules process?
Endogenous antigens are TARGETED for Degradation by the PROTEOSOME by UBIQUITINATION
How do Class 1 molecules present ENDOGENEOUS antigens?
1 - Antigens are produced inside cell (Virus DNA)
2 - MHC Class 1 molecules collect PEPTIDES derived from PROTEINS made in the CYTOSOL
3 - Following Trafficking, Class 1 presents antigens on cell surface
4 - Antigens recognises by the CD8+ cytotoxic T Cell which destroys the virally affected cell.
What does UBIQUITINATION entail?
During Infection IFNy induces 2 proteosome enzyme subunits
LMP2
LMP7
Which generate PEPTIDES which bind to MHC CLASS 1
How are antigen peptides transported (Class 1)?
Along the Endoplasmic Reticulum (ER) the antigen peptides are TRANSPORTED by TAP(Transporter associated with Antigen Processing)
How do Class 2 molecules present EXOGENEOUS antigens?
MHC Class 2 bind peptides made from proteins in the intracellular membrane-bound VESICLES. (Macrophages/B Cells)
Such Peptide-MHC Class 2 are recognised by CD4+ HELPER T CELLS which activate B Cells/Macrophages by
- Release of CYTOKINES
- Cell-Cell contact
What is the process by which Antigens are uptaked called? (Class 2)
ENDOCYTOSIS
What is the Invariant Chain (Ii)?
- Molecule that blocks peptide groove so Class 2 MHC is blocked from binding with ENDOGENEOUS peptides (Class 1)
- Ii-Clip is digested, then MHC Class 2 binds to EXOGENEOUS antigens
How do Class 2 molecules present EXOGENEOUS antigens?
1) Bacteria from outside cell enters and infects MACROPHAGES
2) Bacteria enters VESICLE producing PEPTIDE FRAGMENTS
3) Bacteria Fragments bound by MHC CLASS 2 in vesicles
4) Bound peptides are transported to cell surface
For full activation, T-Cells require additional signals.
What’s are they called?
Costimulation/Priming
Cytokine Signal
What is Costimulation/Priming?
Bidirectional Signalling between cell surface receptor pairs such as
CD80/86 - from APC
CD28 - from T Cell
Give an example of Cytokines introduces by APC to stimulate Effector T Cell differentiation
IL-12
When does APC give these costimulary and Cytokine signals?
When inflammation is present.
What is TCR binding called?
Ligation
What does TCR ligation do?
Prevents AUTOIMMUNITY by TOLERANCE
How can pathogens evade antigen processing?
1) Enter the CYTOPLASM
e. g. LISTERIA
2) Block PHAGOSOME/LYSOSOME fusion
e. g. M. TUBERCULOSIS
3) Degrade MHC Class II
e. g. LEISHMANIA